Apoptosis of intestinal intraepithelial lymphocytes induced by exogenous and endogenous glucocorticoids.

Abstract

To investigate the effect of glucocorticoids on apoptosis in intestinal intraepithelial lymphocytes (i-IEL), we examined the changes of i-IEL followed by in vivo treatment with dexamethasone. The fragmented DNA of i-IEL were significantly increased at 15 hr after dexamethasone treatment and, subsequently, the number of total i-IEL were decreased by day 4 after treatment. Although all subsets of i-IEL including CD8 alpha/alpha(+), CD8 alpha/beta(+), CD4+ and CD4+CD8+ i-IEL were decreased after dexamethasone treatment, CD8 alpha/alpha(+) i-IEL appeared to be relatively resistant to dexamethasone-induced apoptosis. Consistent with the in vivo findings, CD8 alpha/alpha(+) i-IEL exhibited less susceptibility to dexamethasone-induced cell death in vitro than other subsets. To investigate whether this process occurs under physiological conditions, we examined the kinetics of i-IEL after treatment with 15-hr water immersion stress. In mice subjected to water immersion stress, plasma glucocorticoids were remarkably elevated soon after the 15-hr stress. The increase in the fragmented DNA of i-IEL and subsequent decrease in the number of i-IEL were observed in the stressed mice in the same kinetics as seen in the dexamethasone-treated mice. Similar to dexamethasone-induced ell death, CD8 alpha/alpha(+) i-IEL appeared to be relatively resistant to stress-induced apoptosis compared with other i-IEL subsets. The expression level of Bcl-2 was significantly higher in CD8 alpha/alpha(+) i-IEL than in CD8 alpha/beta(+) i-IEL. Our results indicate that i-IEL are subjected to cell death via apoptosis by exogenous and endogenous glucocorticoids and that different sensitivity to steroid-induced apoptosis may exist among i-IEL subsets in relation to their Bcl-2 expression.